Uterine cancer New subtypes of uterine cancer tumours have been discovered through a large international genetic analysis of the disease that kills thousands of women worldwide each year.

The find could lead to a new classification system for uterine cancer resulting in different treatment options for patients as the subtypes are expected to respond differently to current therapies.

The multicentre study funded by the US National Institutes of Health, published today in the journal Nature, will also help researchers in developing personalised drugs to treat the disease.

"We used to think of uterine cancer as having two subtypes but this new study shows there are actually four molecular subtypes and they go across traditional boundaries of grade," says one of the authors of the new study, cancer cell biologist Dr Pam Pollock from the Queensland University of Technology.

"Each of these subtypes looks really different and would respond differently to different drugs. In the long term we are going to have to molecularly characterise everybody's tumour and hopefully match that to the therapy that we know best treats that subtype."

In Australia, around 2000 women a year are diagnosed with uterine (also called endometrial) cancer. While most cases are picked up early due to spotting in post-menopausal women, nearly 400 women a year die from the disease.

Pollock says to date uterine cancer has been classified as either 'uterine serous' or 'endometrioid' tumours, based on how it appears under the microscope.

She says uterine serous tumours make up just 10 per cent of uterine cancers but are responsible for 40 per cent of deaths because they are more aggressive.

"They have a much poorer prognosis and so they've always been treated more aggressively."

By contrast, says Pollock, the less aggressive endometrioid tumours make up 80 per cent of uterine cancers and are responsible for 50 per cent of deaths.

To date she says endometrioid tumours have been classified as being low, moderate or high grade.

But the latest research suggests this classification system needs to be revised.

Molecular reclassification

Pollock and colleagues took samples from 373 endometrial cancers from all over the world, which had been classified according to the current system, and mapped their differences in DNA and protein expression and regulation.

"There are actually three subtypes of endometrioid tumours that don't have anything to do with grade."

Pollock says all grade 3 endometrioid tumours are usually treated aggressively as a precursor to serous tumours but these findings show 75 per cent of grade 3 tumours actually behave like grade 1 and grade 2 tumours, which have a better prognosis.

"The grade 3 tumours are a mix of good and bad prognosis," she says.

Implications

But Pollock says the findings won't immediately change how cancers are diagnosed or treated.

For a start, the technology used by the researchers to classify is not yet available in pathology laboratories.

"The way we've classified them is with extensive genomic platforms that are really expensive. The study would have cost millions and millions of dollars," says Pollock.

For now, she says, the main implications of the findings will be the development of more effective drugs.

Endometrial cancer drugs are traditionally tested on all patients but usually only work in a small percentage of people, says Pollock.

"Overall the drugs fail."

She says scientists can use the latest research to investigate completed trials and find out which subtype of cancer the drug actually worked on and develop better-designed trials.

"Maybe one of these subtypes will have a remarkable response and others won't but we won't know that until we analyse cancers by subtype."

Eventually, says Pollock, clinical trials should be carried out for each cancer subtype.

She says the latest research identified new therapeutic targets in the serous subtype of uterine cancer, for which there are already drugs available.

"The next step will be to do clinical trials just in those patients with each new drug target to see if they respond to these new drugs."

Pollock stresses early detection of uterine cancer is important and postmenopausal women with any bleeding should see their doctor as soon as possible.